Biomedical subjects
Publications and source records attributed to R Müller.
Transfer of mouse or human c-fos proto-oncogenes into F9 teratocarcinoma stem cells results in expression of c-fos mRNA and protein. This is accompanied by the appearance of morphologically altered cells which express several specific markers characteristic of differentiated cells, suggesting that c-fos plays a role in cellular differentiation.
Stimulation of fibroblasts with serum or purified growth factors leads to a dramatic induction of expression of both c-fos mRNA and protein within a few minutes, followed by activation of c-myc. This suggests that c-fos induction is a primary event and the earliest known effect on gene expression by growth factors.
Previous studies have suggested a role for c-fos in cellular differentiation in fetal membranes, haematopoietic cells and teratocarcinoma stem cells. In other cell types, such as fibroblasts, c-fos expression is normally very low, but is rapidly induced by peptide growth factors, implicating c-fos in growth control mechanisms. Here, we show that the TPA (12-O-tetradecanoylphorbol-13-acetate)-induced macrophage-like differentiation of HL60 human promyelocytic precursor cells is accompanied by the induction of both c-fos mRNA and protein within 15 min after treatment, suggesting a functional role for c-fos in this differentiation system. In quiescent terminally differentiated macrophages, expression of c-fos is inducible by the macrophage-specific growth factor colony-stimulating factor-1 (CSF-1). The kinetics of c-fos induction, however, are entirely different from those in growth factor-stimulated fibroblasts, supporting the view that the c-fos gene product may serve different functions in different cell types.
Transgenic mice were generated expressing c-fos genes under the control of the human metallothionein promoter. Although high levels of c-fos messenger RNA were detectable in a variety of tissues, deregulated c-fos expression specifically interfered with normal bone development without inducing malignant tumours.
PURPOSE OF THE STUDY: Little is known about the effect of a tumor on the trabecular architecture, therefore we employed an animal model for the assessment of bone quality in tumor osteolysis to determine the alterations of the trabecular architecture in tumor osteolysis and after an interventional treatment with a bisphosphonate. METHODS: To assess the bone mass and the micro-architecture of the trabecular bone in tumor osteolysis we employed a micro-computed tomography system. For the assessment of the mechanical properties of the treated and non-treated tumor-bearing bones we used a torsion test. RESULTS: The presence of a tumor in bone resulted in a reduction of bone mass, stability and architectural parameters. An interventional treatment of the animals with a bisphosphonate increased the bone mineral content, mechanical and architectural parameters compared to the non-treated, tumor-bearing animals. CONCLUSIONS: These results clearly show a beneficial effect of an anti-osteolytic treatment with a bisphosphonate in regard of bone quality in tumor-induced osteolysis.
In Germany there are only insufficient data both with regard to general morbidity events as well as with regard to the effects of specific professions on the morbidity process. For this reason the data of the Gmuender Ersatzkasse (GEK) have been analysed with a longitudinal design for the period 1990 to 2003. Our sample includes all employed members of the GEK who had been insured as of January 1, 1990 and were between 30 and 59 years old at this baseline. The total sample comprises 129,173 men and 13,567 women. The statistical analysis was performed with the statistical package "Transitional Data Analysis" (TDA) which was developed especially for longitudinal data. The analysis includes both cumulated morbidity rates as well as transition rates (Cox regression). The analysis shows that the cumulated morbidity rates of the seven diseases are higher for women than for men in the age category 30-39 years. In the age categories 40-49 and 50-59 years the cumulated morbidity rates are higher for men than for women. With regard to the occupations, the highest morbidity rates are found for manual occupations and services without special skills. The lowest rates are found for professions with high skills, engineers and managers. The results of the longitudinal analysis show distinctive social gradients. For occupations with lower skills the morbidity rates are about 100 percent higher than those of occupations with higher skills. Longitudinal analyses on the basis of health insurance fund data can make an important contribution to the monitoring of health and morbidity and should therefore be conducted also by other health insurance funds.
This report describes the ultrasonographic and radiographic findings and the treatment of a Swiss Brown cow with a retropharyngeal abscess caused by improper administration of a magnet.
156 patients with transient ischemic attacks (TIA) or reversible ischemic neurological deficit (RIND) were given prophylactic anticoagulant (AC) treatment against cerebral infarction in a prospective multicenter study from 5 hospitals in southern Sweden. After 2 months of AC treatment, 135 patients remained in the study and were randomized into 2 groups; one continued with AC treatment and one changed to anti-platelet therapy. The patients were followed for 12 months. No significant difference was seen between the 2 groups but 3 completed cerebral infarctions occurred during anti-platelet therapy against one during AC treatment. One cerebral hemorrhage was seen during AC treatment. All completed strokes occurred in men who initially had carotid symptoms. The number of patients with TIA/RIND was somewhat higher in the anti-platelet group whereas myocardial infarctions occurred more often during AC treatment. Compared to the natural history of untreated TIA/RIND both treatments were found to have a prophylactic effect against cerebral infarction.
One hundred seventy-eight patients with transient ischemic attacks (TIAs) or small strokes with slight symptoms persisting for more than 24 hours (incomplete recovery = IR) (TIA-IR) from both the carotid and the vertebrobasilar systems were treated with anticoagulants. Ten patients stopped the treatment because of severe side effects. Only one patient had a lethal cerebral infarction when the thrombotest values were above the therapeutic level; no other infarction happened during the treatment period. Moreover, the frequency of TIA decreased during the treatment, compared with descriptions of the natural course of TIA. One hundred four patients were observed for a mean of 21 months after the anticoagulant treatment ended. During the observation period, six patients had cerebral infarctions. This was a sixfold increase compared with the stroke incidence during treatment, and was almost identical with the incidence of strokes seen during the natural course of TIA. All the cerebral infarctions were in patients who had their initial TIA/TIA-IR from the carotid territory (within the same carotid artery which earlier had given symptoms). The investigation shows that long-term anticoagulant treatment is useful, especially in patients with carotid TIA/TIA-IR, and that this treatment should continue as long as the patients can manage it. In patients with vertebrobasilar symptoms of malignant character, it seems feasible to terminate the treatment after about one year. The mechanism of the anticoagulant treatment is obscure, but it does not appear to influence the progress of the atherosclerotic process.
Nine severely injured patients (SIP) and 9 healthy controls received 20 min iv infusions of Aminoplasmal-LS-10 (2.15 ml/kg body wt containing 0.215 g amino acids). Employing the values of the plasma amino acid (AA) concentrations 3, 7, 15, 30, 45, 70, and 150 min after the end of the infusion, we calculated the elimination half-life (t 1/2), the elimination constant (k2), the total clearance (Cltot), and the transfer of the individual AA. The AA showed t 1/2 between 6 (Glu) and 23 (Thr) min. Comparing the metabolic kinetics of healthy controls and SIP, there were no statistical differences in t 1/2 or in k2. In the SIP, nearly all plasma AA showed increased transfer and Cltot, significantly for Thr (p < 0.05), Pro, Gly, Ala, Arg (p < 0.02), Glu (p < 0.01), and Met (p < 0.005). In contrast, the Cltot for Phe and Tyr were decreased. Except for Phe, Tyr, Met (enhanced values) and Arg (no change), the fasting values of AA concentrations in the SIP were diminished compared to those in the healthy controls. Based on the measured transfer, we have developed a new maintenance solution adapted to SIP. Compared with Aminoplasmal, it is necessary to apply AA concentrations which are increased in Lys, His, Phe, Tyr, Val, Ala, and Ser, and reduced in Arg, Pro, Leu, Ile, and Gly.
Explore the source record for details and available documents.
In order to compare the kinetics of their enzymatic elimination from the DNA of liver, kidney, lung, and brain, the alkylation products O4-ethyl-2'-deoxythymidine (O4-EtdThd) and O6-ethyl-2'-deoxyguanosine (O6-EtdGuo) were quantitated by competitive radioimmunoassay over a period of 48 h after a single pulse of the carcinogen N-ethyl-N-nitrosourea (EtNU) applied i.p. to 10 and 28-day-old BDIX-rats. The content of O4-EtdThd in the DNA of all organs analyzed remained stable, while O6-EtdGuo (initially formed in DNA with 3-4 times higher frequency than O4-EtdThd) was rapidly removed from the DNA of liver, followed by lung and kidney, but persisted strongly in the DNA of brain. At 48 h after the EtNU-pulse, the O4-EtdThd content of liver DNA exceeded the O6-EtdGuo content by about a factor of 4. Since both O6-EtdGuo and O4-EtdThd are miscoding DNA lesions, the lack of enzymatic removal of O4-EtdThd is surprising in view of the apparent concern of cells to restore the integrity of the O6-position of guanine. Genetic consequences more specifically connected with the formation of O6-alkylguanine in DNA might be considered, e.g., possible alterations of gene expression via interference with enzymatic 5-cytosine methylation in 5'-CpG-3' sequences of newly replicated DNA.
Skin hydration can be influenced to a great extent by occlusive compounds. Conventional highly occlusive compounds tend to have an unacceptable appearance. Therefore, the development of innovative occlusive topicals is an essential issue regarding the formulation of cosmetic and pharmaceutical preparations. Solid lipid nanoparticles (SLN) represent a novel carrier system for controlled release of topical cosmetic and pharmaceutical compounds. In addition to their controlled release characteristics, it has been found that SLN have an occlusive effect. The extent of the occlusive effect depends on various factors such as particle size, applied sample volume, lipid concentration, and crystallinity of the lipid matrix. These factors have been investigated in detail by an in vitro test, and the obtained data give insight into their importance.
In our laboratory, the gene transfer efficiency of some lipofection reagents (lipofectine, lipofectamine, DOTAP and Dosper) and histones H3 and H4 was compared to that of DEAE-Dextran (64). The histones H3 and H4 were found to have the highest transfection efficiency of all the agents tested. In the present study we have analyzed other parameters important for gene delivery by the histones H3 and H4. We transferred the HIV-1 tat gene to Jurkat cells and measured the transactivation of HIV-1-LTR by the transactivator protein, expressed in Jurkat cells. The expression of CAT as a reporter gene hybridized to LTR was a direct measure of transactivation potential. In order to investigate whether the transfection was only due to the positive ionic character of the histones H3 and H4 we tested other histones (H1 and H2A) and polylysine in our system. Under our experimental conditions, neither polylysine, nor the histones H1 and H2A were able to promote gene transfer in Jurkat cells. The inability of these reagents to promote gene transfer was not dependent on DNA condensation; in EMSA (Electrophoretic Mobility Shift Assay) all these reagents exhibited a strong retardation of DNA. In the presence of anti-histone-IgG the transfection potential of histones H3 and H4 was diminished in a concentration - dependent manner. To investigate whether the histone antibodies inhibited the condensation of DNA by histones we carried out gel retardation assays (EMSA) in the absence and in the presence of histone antibodies. Anti-histone-IgG had no effect on the retardation of histone-DNA complexes; on the contrary, retardation was increased. This observation has led us to postulate two models for the possible mechanism by which the histones H3 and H4 catalyze gene transfer in eucaryotic cells.
BACKGROUND: Since tumor markers can be increased in the course of many benign diseases, the aim of this study was to verify if this also occurs in the course of rheumatic diseases. MATERIALS AND METHODS: We investigated the incidence and characteristics of Tumor M2-PK in the EDTA-plasma of 137 patients suffering from rheumatic diseases. RESULTS: The tumor M2-PK concentration was increased in 52 out of 63 patients (82%) with classical rheumatoid arthritis, in 15 out of 21 patients (71%) with systemic lupus erythematosus, in 14 out of 17 patients (82%) with seronegative spondylarthritis and in 13 out of 28 patients with miscellaneous rheumatic diseases (46%). Malignant neoplasm was not detected in any of the patients with rheumatic diseases. CONCLUSION: These results demonstrated that the EDTA-plasma concentrations of Tumor M2-PK were increased in patients with rheumatic diseases.
Bacteria with the ability to grow on pyrazon as sole source of carbon were isolated from soil. They also are able to grow on antipyrin. Then three metabolites of antipyrin can be isolated from the culture fluid which were identified as 2,3-dimethyl-1-(cis-2,3-dihydro-2,3-dihydroxy-4,6-cyclohexadiene-1-yl)-pyrazolone (5) (I), as 2,3-dimethyl-1-(2,3-dihydroxyphenyl)-pyrazolone (5) (II) and as 2,3-dimethyl-pyrazolone (5) (III), respectively. Compound I and II were used as substrates for enzyme studies. A dioxygenase catalyzes the enzymatic conversion of antipyrin into compound I. In the presence of NAD as cosubstrate compound I is transformed into compound II by a dehydrogenase. A pure preparation of metapyrocatechase from pyrazon-degrading bacteria converts compound II into the dephenylated heterocyclic moiety of antipyrin (III) and into 2-pyrone-6-carboxylic acid. Based on the results of the enzymatic studies a pathway for the degradation of antipyrin is proposed.
In children, the nephrotic syndrome is usually corticoid-responsive; approximately 70% of patients experience relapses, frequently triggered by infections. Our paper presents the results obtained using a 4 month prednisone regimen. This retrospective study included 83 children afflicted with nephrotic syndrome over a 10 year span. We analyzed: age at diagnosis, boys/girls ratio, response to corticoid treatment - after one month of prednisone and at the completion of the treatment course, number of relapses and their frequency, complications of prednisone treatment. The median age at diagnosis was 4.8 years, males predominating M:F = 1.5:1. Complete response after 4 weeks of prednisone therapy was noted in 98.79% of cases. We had 116 episodes of relapses during the first year of follow-up, occurring in 67.4% of children (27.9% were frequent relapsers, 11.62% subsequently became corticoid-dependent). Late relapses, after the first year, occurred in 32.55% of cases. We noted mostly mild adverse effects of the prednisone treatment: occurrence of infections during therapy (16.27%), cushingoid facies (37.2%), hirsutism (4.6%), high blood pressure (4.65%), stretch marks (2.32%). In conclusion, the 4 month prednisone treatment regimen is efficient in inducing and maintaining a remission. The incidence of relapses is 32.55%, comparable to the figure cited in larger studies. Serious adverse effects are significantly lower with this regimen compared to other corticoid treatment schemes. Key wo
A boronated analogue of the antiestrogen U 23,469-M (D. Lednicer, D. W. Emmert, S. C. Lyster, and G. W. Duncan, J. Med. Chem. 12, 881 (1969] was prepared, for possible use in neutron capture therapy of estrogen receptor-positive tumors. In this analogue, the terminal OH group was replaced by a B-decachloro-o-carboranyl residue. This compound showed a large, non-specific uptake in ZR 75-1 breast cancer-derived cells. It could partially inhibit the uptake of estradiol in these cells. Accumulation in the cells at physiologically obtainable concentrations was, however, too low to envisage a therapeutic effect following thermal neutron irradiation.